The comparative effect of pioglitazone and metformin on serum osteoprotegerin, adiponectin and intercellular adhesion molecule concentrations in patients with newly diagnosed type 2 diabetes: a randomized clinical trial

Exp Clin Endocrinol Diabetes. 2015 May;123(5):289-95. doi: 10.1055/s-0034-1396864. Epub 2015 Jan 21.


Aim: The etiologic role of inflammatory pathways in the development of diabetic complications, especially cardiovascular events, has been established. The anti-inflammatory role of metformin and pioglitazone has been described; however, no study to date has compared the efficacy of these common oral agents in this regard. In this study, the authors aimed to compare the anti-inflammatory properties of pioglitazone and metformin, with respect to their effect on serum concentrations of highly sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG), intercellular adhesion molecule-1 (ICAM-1) and adiponectin.

Methods: In an open-label randomized clinical trial, 117 patients with newly diagnosed type 2 diabetes mellitus were visited; 84 fulfilled the inclusion criteria, and were randomly allocated to 2 arms receiving either 1,000 mg/d metformin or 30 mg/d pioglitazone, respectively. Biochemical assessments were made at baseline and the end of the 3 months trial.

Results: Significant reduction in FPG, insulin and HbA1c in women and men of both arms were observed. Log-hsCRP values significantly decreased in both arms. A decreasing, but non-significant trend in log-OPG levels was observed in women of the metformin arm (p=0.063). A greater reduction in log-ICAM levels was identifiable in men receiving pioglitazone compared to the other arm (p=0.008); in addition, the same trend was observed in log-OPG values (p=0.029). Nonetheless, reduction in log-ICAM and log-OPG levels was comparable between the 2 arms. A significant increase in adiponectin was observed in both men and women in the pioglitazone arm (p<0.001), whereas changes were non-significant in the metformin arm.

Conclusion: Remarkably, patients receiving pioglitazone revealed more significant reduction in inflammatory markers.

Trial registration: NCT01963663.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adiponectin / agonists
  • Adiponectin / blood
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Blood Glucose / analysis
  • C-Reactive Protein / analysis
  • C-Reactive Protein / antagonists & inhibitors
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / immunology
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hyperglycemia / prevention & control
  • Hypoglycemic Agents / therapeutic use*
  • Inflammation Mediators / agonists
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / blood*
  • Intercellular Adhesion Molecule-1 / blood
  • Intercellular Adhesion Molecule-1 / chemistry
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Osteoprotegerin / antagonists & inhibitors
  • Osteoprotegerin / blood
  • Pioglitazone
  • Sex Characteristics
  • Thiazolidinediones / therapeutic use*


  • ADIPOQ protein, human
  • Adiponectin
  • Anti-Inflammatory Agents, Non-Steroidal
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • ICAM1 protein, human
  • Inflammation Mediators
  • Osteoprotegerin
  • TNFRSF11B protein, human
  • Thiazolidinediones
  • hemoglobin A1c protein, human
  • Intercellular Adhesion Molecule-1
  • C-Reactive Protein
  • Metformin
  • Pioglitazone

Associated data